Hyperbaric oxygen (HBO) has been used for treatment of conditions involving oxygenation accidents as seen in scuba diving and high altitude sports activities like mountain climbing. We demonstrate in the present study that HBO is potentially therapeutic for ameliorating post-ischemic stroke symptoms. Adult Sprague-Dawley rats received middle cerebral artery occlusion (MCAo) for 1 hour, and thereafter animals were introduced to: a) immediate 1 hour HBO (3 atm) or 1 hour hyperbaric pressure (HBP, 3 atm); b) 1 hour delay, which corresponded to 1 hour reperfusion, prior to 1 hour HBO or HBP treatment; or c) no treatment at all. Behavioral examination using the elevated body swing test at 24 and 48 hours after reperfusion revealed that almost all animals exposed to immediate HBO did not display biased swing activity, a few animals in the 1 hour delay HBO and immediate HBP treatment groups also exhibited near symmetrical swing activity, whereas all the animals in the delayed HBP treatment and in the no treatment groups showed asymmetrical response. At 48 hours after reperfusion, triphenyltetrazolium chloride staining revealed that animals exposed to immediate HBO treatment showed no detectable brain infarction: a few animals in the delayed HBO and immediate HBP treatment groups also exhibited absence of brain infarction, but the rest of the animals displayed the characteristic brain infarction produced by MCAo. The present results indicate the efficacy of HBO and, to some extent, by early HBP in ameliorating ischemia-induced brain damage and behavioral dysfunctions, which are not fully addressed by current therapeutic strategies for stroke. (Supported by National Defense Medical Center, Taiwan). - Stroke